Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2018

Open Access 01-12-2018 | Research article

Proteomic profiling of senescent human diploid fibroblasts treated with gamma-tocotrienol

Authors: Jen-Kit Tan, Faizul Jaafar, Suzana Makpol

Published in: BMC Complementary Medicine and Therapies | Issue 1/2018

Login to get access

Abstract

Background

Replicative senescence of human diploid fibroblasts (HDFs) has been used as a model to study mechanisms of cellular aging. Gamma-tocotrienol (γT3) is one of the members of vitamin E family which has been shown to increase proliferation of senescent HDFs. However, the modulation of protein expressions by γT3 in senescent HDFs remains to be elucidated. Therefore, this study aimed to determine the differentially expressed proteins (DEPs) in young and senescent HDFs; and in vehicle- and γT3-treated senescent HDFs using label-free quantitative proteomics.

Methods

Whole proteins were extracted and digested in-gel with trypsin. Peptides were detected by Orbitrap liquid chromatography mass spectrometry. Mass spectra were identified and quantitated by MaxQuant software. The data were further filtered and analyzed statistically using Perseus software to identify DEPs. Functional annotations of DEPs were performed using Panther Classification System.

Results

A total of 1217 proteins were identified in young and senescent cells, while 1218 proteins in vehicle- and γT3-treated senescent cells. 11 DEPs were found in young and senescent cells which included downregulation of platelet-derived growth factor (PDGF) receptor beta and upregulation of tubulin beta-2A chain protein expressions in senescent cells. 51 DEPs were identified in vehicle- and γT3-treated senescent cells which included upregulation of 70 kDa heat shock protein, triosephosphate isomerase and malate dehydrogenase protein expressions in γT3-treated senescent cells.

Conclusions

PDGF signaling and cytoskeletal structure may be dysregulated in senescent HDFs. The pro-proliferative effect of γT3 on senescent HDFs may be mediated through the stimulation of cellular response to stress and carbohydrate metabolism. The expressions and roles of these proteins in relation to cellular senescence are worth further investigations. Data are available via ProteomeXchange with identifier PXD009933.
Appendix
Available only for authorised users
Literature
1.
Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 1965;37(3):614–36.CrossRef
2.
Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai EV, Futcher AB, et al. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci U S A. 1992;89(21):10114–8.CrossRef
3.
Goon JA, Ahmad Hairi H, Makpol S, Abdul Rahman M, Karsani SA, Wan Ngah WZ. Differential protein expression in senescent human skin fibroblasts and stress induced premature senescence (SIPS) fibroblasts. Sains Malaysiana. 2011;40(11):1247–53.
4.
Trougakos IP, Saridaki A, Panayotou G, Gonos ES. Identification of differentially expressed proteins in senescent human embryonic fibroblasts. Mech Ageing Dev. 2006;127(1):88–92.CrossRef
5.
Cong YS, Fan E, Wang E. Simultaneous proteomic profiling of four different growth states of human fibroblasts, using amine-reactive isobaric tagging reagents and tandem mass spectrometry. Mech Ageing Dev. 2006;127(4):332–43.CrossRef
6.
Hammad G, Legrain Y, Touat-Hamici Z, Duhieu S, Cornu D, Bulteau AL, et al. Interplay between selenium levels and replicative senescence in WI-38 human fibroblasts: a proteomic approach. Antioxidants. 2018;7(1):19.
7.
Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298–300.CrossRef
8.
Sen CK, Khanna S, Roy S. Tocotrienols: vitamin E beyond tocopherols. Life Sci. 2006;78(18):2088–98.CrossRef
9.
Goon JA, Mohd Adi M, Ahmad Hairi H. Tocotrienol rich fraction (TRF) increases viability of senescent fibroblast. Research Updates in Medical Sciences. 2013;1(2):3–6.
10.
Makpol S, Yeoh TW, Ruslam FA, Arifin KT, Yusof YA. Comparative effect of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction on antioxidant enzymes activity in cellular ageing of human diploid fibroblasts. BMC Complement Altern Med. 2013;13:210.CrossRef
11.
Makpol S, Durani LW, Chua KH, Mohd Yusof YA, Ngah WZ. Tocotrienol-rich fraction prevents cell cycle arrest and elongates telomere length in senescent human diploid fibroblasts. J Biomed Biotechnol. 2011;2011:506171.CrossRef
12.
Makpol S, Abidin AZ, Sairin K, Mazlan M, Top GM, Ngah WZ. Gamma-tocotrienol prevents oxidative stress-induced telomere shortening in human fibroblasts derived from different aged individuals. Oxidative Med Cell Longev. 2010;3(1):35–43.CrossRef
13.
Makpol S, Zainuddin A, Chua KH, Yusof YA, Ngah WZ. Gamma-tocotrienol modulation of senescence-associated gene expression prevents cellular aging in human diploid fibroblasts. Clinics. 2012;67(2):135–43.CrossRef
14.
Makpol S, Zainuddin A, Chua KH, Mohd Yusof YA, Ngah WZ. Gamma-tocotrienol modulated gene expression in senescent human diploid fibroblasts as revealed by microarray analysis. Oxidative Med Cell Longev. 2013;2013:454328.
15.
Zainuddin A, Chua KH, Tan JK, Jaafar F, Makpol S. Gamma-tocotrienol prevents cell cycle arrest in aged human fibroblast cells through p16(INK4a) pathway. J Physiol Biochem. 2017;73(1):59–65.CrossRef
16.
Shevchenko A, Tomas H, Havlis J, Olsen JV, Mann M. In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc. 2006;1(6):2856–60.CrossRef
17.
Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008;26(12):1367–72.CrossRef
18.
The UniProt C. UniProt: the universal protein knowledgebase. Nucleic Acids Res. 2017;45(D1):D158–D69.CrossRef
19.
Tyanova S, Temu T, Sinitcyn P, Carlson A, Hein MY, Geiger T, et al. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat Methods. 2016;13(9):731–40.CrossRef
20.
Thomas PD, Campbell MJ, Kejariwal A, Mi H, Karlak B, Daverman R, et al. PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 2003;13(9):2129–41.CrossRef
21.
Vizcaino JA, Csordas A, Del-Toro N, Dianes JA, Griss J, Lavidas I, et al. 2016 update of the PRIDE database and its related tools. Nucleic Acids Res. 2016;44(22):11033.CrossRef
22.
Heldin CH, Lennartsson J. Structural and functional properties of platelet-derived growth factor and stem cell factor receptors. Cold Spring Harb Perspect Biol. 2013;5(8):a009100.CrossRef
23.
Mori S, Kawano M, Kanzaki T, Morisaki N, Saito Y, Yoshida S. Decreased expression of the platelet-derived growth factor beta-receptor in fibroblasts from a patient with Werner's syndrome. Eur J Clin Investig. 1993;23(3):161–5.CrossRef
24.
Chen JH, Ozanne SE, Hales CN. Analysis of expression of growth factor receptors in replicatively and oxidatively senescent human fibroblasts. FEBS Lett. 2005;579(28):6388–94.CrossRef
25.
Li Q, Bai L, Liu N, Wang M, Liu JP, Liu P, et al. Increased polymerase I and transcript release factor (Cavin-1) expression attenuates platelet-derived growth factor receptor signalling in senescent human fibroblasts. Clin Exp Pharmacol Physiol. 2014;41(3):169–73.CrossRef
26.
Smith R, Bacos K, Fedele V, Soulet D, Walz HA, Obermuller S, et al. Mutant huntingtin interacts with {beta}-tubulin and disrupts vesicular transport and insulin secretion. Hum Mol Genet. 2009;18(20):3942–54.CrossRef
27.
Herve JC, Bourmeyster N. Rho GTPases at the crossroad of signaling networks in mammals. Small GTPases. 2015;6(2):43–8.CrossRef
28.
Lehmann SG, Bourgoin-Voillard S, Seve M, Rachidi W. Tubulin beta-3 chain as a new candidate protein biomarker of human skin aging: a preliminary study. Oxidative Med Cell Longev. 2017;2017:5140360.CrossRef
29.
Lackie RE, Maciejewski A, Ostapchenko VG, Marques-Lopes J, Choy WY, Duennwald ML, et al. The Hsp70/Hsp90 chaperone machinery in neurodegenerative diseases. Front Neurosci. 2017;11:254.CrossRef
30.
Bobkova NV, Evgen'ev M, Garbuz DG, Kulikov AM, Morozov A, Samokhin A, et al. Exogenous Hsp70 delays senescence and improves cognitive function in aging mice. Proc Natl Acad Sci U S A. 2015;112(52):16006–11.CrossRef
31.
Gutsmann-Conrad A, Heydari AR, You S, Richardson A. The expression of heat shock protein 70 decreases with cellular senescence in vitro and in cells derived from young and old human subjects. Exp Cell Res. 1998;241(2):404–13.CrossRef
32.
Anderson RM, Weindruch R. Metabolic reprogramming, caloric restriction and aging. Trends Endocrinol Metab. 2010;21(3):134–41.CrossRef
33.
Wiley CD, Campisi J. From ancient pathways to aging cells-connecting metabolism and cellular senescence. Cell Metab. 2016;23(6):1013–21.CrossRef
34.
Orosz F, Olah J, Ovadi J. Triosephosphate isomerase deficiency: new insights into an enigmatic disease. Biochim Biophys Acta. 2009;1792(12):1168–74.CrossRef
35.
Zhao L, Jia Y, Yan D, Zhou C, Han J, Yu J. Aging-related changes of triose phosphate isomerase in hippocampus of senescence accelerated mouse and the intervention of acupuncture. Neurosci Lett. 2013;542:59–64.CrossRef
36.
Ziegler DV, Wiley CD, Velarde MC. Mitochondrial effectors of cellular senescence: beyond the free radical theory of aging. Aging Cell. 2015;14(1):1–7.CrossRef
37.
Lee SM, Dho SH, Ju SK, Maeng JS, Kim JY, Kwon KS. Cytosolic malate dehydrogenase regulates senescence in human fibroblasts. Biogerontology. 2012;13(5):525–36.CrossRef
Metadata
Title
Proteomic profiling of senescent human diploid fibroblasts treated with gamma-tocotrienol
Authors
Jen-Kit Tan
Faizul Jaafar
Suzana Makpol
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2018
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-018-2383-6

Other articles of this Issue 1/2018

BMC Complementary Medicine and Therapies 1/2018 Go to the issue

Research article

Antibacterial interactions, anti-inflammatory and cytotoxic effects of four medicinal plant species

Research article

Perceptions of traditional Chinese medicine for chronic disease care and prevention: a cross-sectional study of Chinese hospital-based health care professionals

Research article

Polyphenols of Salix aegyptiaca modulate the activities of drug metabolizing and antioxidant enzymes, and level of lipid peroxidation

Research article

The use of complementary and alternative medicine by patients with cancer: a cross-sectional survey in Saudi Arabia

Research article

Zerumbone from Zingiber zerumbet (L.) smith: a potential prophylactic and therapeutic agent against the cariogenic bacterium Streptococcus mutans

Research article

Prescription patterns of traditional Chinese medicine amongst Taiwanese children: a population-based cohort study